On the Distinction Between Lag and Delay in Population Growth

The analysis and results presented in this paper provide conclusive evidence to distinguish between the delay effect and the lag as two biologically distinct phenomena. It therefore dispels the incorrect notion that delay effects represented by delay differential equations are the biological reason behind the lag phase in microorganism growth. The resulting consequence so far is that the only other reason for the lag phase is the existence of unstable stationary states. The latter are a result of accounting for the microbial metabolic mass transfer in the population growth process.     

Community Attitudes and Practices of Urban Residents Regarding Predation by Pet Cats on Wildlife: An International Comparison

International differences in practices and attitudes regarding pet cats'' interactions with wildlife were assessed by surveying citizens from at least two cities in Australia, New Zealand, the UK, the USA, China and Japan. Predictions tested were: (i) cat owners would agree less than non-cat owners that cats might threaten wildlife, (ii) cat owners value wildlife less than non-cat owners, (iii) cat owners are less accepting of cat legislation/restrictions than non-owners, and (iv) respondents from regions with high endemic biodiversity (Australia, New Zealand, China and the USA state of Hawaii) would be most concerned about pet cats threatening wildlife. Everywhere non-owners were more likely than owners to agree that pet cats killing wildlife were a problem in cities, towns and rural areas. Agreement amongst non-owners was highest in Australia (95%) and New Zealand (78%) and lowest in the UK (38%). Irrespective of ownership, over 85% of respondents from all countries except China (65%) valued wildlife in cities, towns and rural areas. Non-owners advocated cat legislation more strongly than owners except in Japan. Australian non-owners were the most supportive (88%), followed by Chinese non-owners (80%) and Japanese owners (79.5%). The UK was least supportive (non-owners 43%, owners 25%). Many Australian (62%), New Zealand (51%) and Chinese owners (42%) agreed that pet cats killing wildlife in cities, towns and rural areas was a problem, while Hawaiian owners were similar to the mainland USA (20%). Thus high endemic biodiversity might contribute to attitudes in some, but not all, countries. Husbandry practices varied internationally, with predation highest where fewer cats were confined. Although the risk of wildlife population declines caused by pet cats justifies precautionary action, campaigns based on wildlife protection are unlikely to succeed outside Australia or New Zealand. Restrictions on roaming protect wildlife and benefit cat welfare, so welfare is a better rationale.     

Resistance of Human Liver Mesenchymal Stem Cells to FAS-Induced Cell Death

Mesenchymal stem cells (MSCs) have a pronounced therapeutic potential in various pathological conditions. Though therapeutic effects of MSC transplantation have been studied for a long time, the underlying mechanisms are still not clear. It has been shown that transplanted MSCs are rapidly eliminated, presumably by apoptosis. As the mechanisms of MSC apoptosis are not fully understood, in the present work we analyzed MSC sensitivity to Fas-induced apoptosis using MSCs isolated from the biopsies of liver fibrosis patients (L-MSCs). The level of cell death was analyzed by flow cytometry in the propidium iodide test. The luminescent ATP assay was used to measure cellular ATP levels; and the mitochondrial membrane potential was assessed using the potential-dependent dye JC-1. We found that human L-MSCs were resistant to Fas-induced cell death over a wide range of FasL and anti-Fas mAb concentrations. At the same time, intrinsic death signal inducers CoCl₂ and staurosporine caused apoptosis of L-MSCs in a dose-dependent manner. Despite the absence of Fas-induced cell death treatment of L-MSCs with low concentrations of FasL or anti-Fas mAb resulted in a cellular ATP level decrease, while high concentrations of the inducers caused a decline of the mitochondrial membrane potential. Pre-incubation of L-MSCs with the pro-inflammatory cytokine TNF-α did not promote L-MSC cell death. Our data indicate that human L-MSCs have increased resistance to receptor-mediated cell death even under inflammatory conditions.     

Transcriptional profiling of Zea mays roots reveals roles for jasmonic acid and terpenoids in resistance against Phytophthora cinnamomi

Phytophthora cinnamomi is a soil-borne plant pathogen that has caused widespread damage to vulnerable native ecosystems and agriculture systems across the world and shows no sign of abating. Management of the pathogen in the natural environment is difficult and the options are limited. In order to discover more about how resistant plants are able to defend themselves against this generalist pathogen, a microarray study of plant gene expression following root inoculation with P. cinnamomi was undertaken. Zea mays was used as a resistant model plant, and microarray analysis was conducted using the Affymetrix GeneChip Maize Genome Array on root samples collected at 6- and 24-h post-inoculation. Over 300 genes were differentially expressed in inoculated roots compared with controls across the two time points. Following Gene Ontology enrichment analysis and REVIGO visualisation of the up-regulated genes, many were implicated in plant defence responses to biotic stress. Genes that were up-regulated included those involved in phytoalexin biosynthesis and jasmonic acid/ethylene biosynthesis and other defence-related genes including those encoding glutathione S-transferases and serine-protease inhibitors. Of particular interest was the identification of the two most highly up-regulated genes, terpene synthase11 (Tps11) and kaurene synthase2 (An2), which are both involved in production of terpenoid phytoalexins. This is the first study that has investigated gene expression at a global level in roots in response to P. cinnamomi in a model plant species and provides valuable insights into the mechanisms involved in defence.     

A Genetically Encoded Reporter for Real-Time Imaging of Cofilin-Actin Rods in Living Neurons

Filament bundles (rods) of cofilin and actin (1:1) form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP) and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30–60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination.     

The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption

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Highlights? Derepression of HIF-2α mRNA in Irp1^?/? mice causes age-dependent polycythemia ? HIF-2α hyperactivity is observed in multiple tissues of Irp1^?/? mice ? The mRNA regulons of IRP1 and IRP2 are separable in vivo ? The IRP1-HIF-2α axis is a therapeutic target for hematologic or oncologic disorders     

Structural Evaluation and Analyses of Tumor Differentiation Factor

Tumor differentiation factor (TDF) is a protein produced by the pituitary and secreted into the blood stream. The mechanism of its action has still not been elucidated, although the associated protein receptor was identified. Furthermore, the TDF protein does not have any homology with other known proteins, and the crystal structure of TDF also is not available at this time. To gain some insight into the structure of this rather underexplored protein, we have performed a molecular dynamics simulation of a model TDF structure. The structural stability of this protein is evaluated as a function of time. The time dependent structural changes of four cysteine residues present in this structure also are explored.     

Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a Chinese Population

The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10⁻³). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.     

Display of functional nucleic acid polymerase on Escherichia coli surface and its application in directed polymerase evolution

We report a first of its kind functional cell surface display of nucleic acid polymerase and its directed evolution to efficiently incorporate 2′-O-methyl nucleotide triphosphates (2′-OMe-NTPs). In the development of polymerase cell surface display, two autotransporter proteins (Escherichia coli adhesin involved in diffuse adherence and Pseudomonas aeruginosa esterase A [EstA]) were employed to transport and anchor the 68-kDa Klenow fragment (KF) of E. coli DNA polymerase I on the surface of E. coli. The localization and function of the displayed KF were verified by analysis of cell outer membrane fractions, immunostaining, and fluorometric detection of synthesized DNA products. The EstA cell surface display system was applied to evolve KF for the incorporation of 2′-OMe-NTPs and a KF variant with a 50.7-fold increased ability to successively incorporate 2′-OMe-NTPs was discovered. Expanding the scope of cell-surface displayable proteins to the realm of polymerases provides a novel screening tool for tailoring polymerases to diverse application demands in a polymerase chain reaction and sequencing-based biotechnological and medical applications. Especially, cell surface display enables novel polymerase screening strategies in which the heat-lysis step is bypassed and thus allows the screening of mesophilic polymerases with broad application potentials ranging from diagnostics and DNA sequencing to replication of synthetic genetic polymers.